[karen]

I just found a research paper that talks about the Half-life of Miroestrol which I believe is the key phyto-estrogenic compund in PM. It stated that the Half-life of Miroestrol is 3.2 hours in women and 4.2 hours in men.

I played around with a spreadsheet a little ... looking at total blood levels when taking PM every 4 hours, 6, hours, 8 hours, and 12 hours. I used a value of "1" for each capsule (doesn't matter what the real number is since it ends up being proportionate) so after 4 hours (approx) that capsule would then have a value of ".5" in your system ... and after another 4 hours ".25" ... and so on ...

So then when you take the next capsule there is a residual PLUS another value of "1" for the new capsule .... and they are additive ... always adding whats already in your system from a previous capsule or capsules PLUS what is added from a new one.

When you total them and then graph them I thought it was pretty interesting .... as you lengthen the time between capsules two things happen .... the swing between the high lvel in your system and the low level in your system gets wider and wider ... plus any interval longer than 4 hours lower the maximum amount in your systems total ....

I would think you would want to minimize the swing and slowly work your way up to a level that produces the desired results ... I think you would end up taking less capsules each time BUT more frequently ...

Just something to think about

Karen .... and yup I'm still here

[karen]

No-one has any opinions on this subject? Sure has allot of views.

Karen

[flamesabers]

I just found a research paper that talks about the Half-life of Miroestrol which I believe is the key phyto-estrogenic compund in PM. It stated that the Half-life of Miroestrol is 3.2 hours in women and 4.2 hours in men.

Do you have a link to this research paper? Did it explain why minoestrol has a longer half-life in men?

When you total them and then graph them I thought it was pretty interesting .... as you lengthen the time between capsules two things happen .... the swing between the high lvel in your system and the low level in your system gets wider and wider ... plus any interval longer than 4 hours lower the maximum amount in your systems total ....

I would think you would want to minimize the swing and slowly work your way up to a level that produces the desired results ... I think you would end up taking less capsules each time BUT more frequently ...

The swing between the high and low levels of minoestrol in the body makes sense. I'm not sure what you mean by taking less capsules each time but more frequently. Unless I switch from using capsules to powder form, I don't see how else I can further break down my 2,500 mg daily intake. For my routine I take 1,000 mg in the morning, than 500 mg every 4-6 hours until I hit 2,500 mg for the day. If sleep wasn't a factor, are you suggesting it would be more effective for me to take about 100 mg of pm every hour of every day?

[LookingForward2NBE]

The T1/2 (half-life) of a drug you are correct that reflects the time a body requires to eliminate (or deactivate is better representation of what actually happens) 1/2 of the drug from your system.

Here are some important things to take into consideration when looking at T1/2:

1. You need to know what the ED50 (effective dose in 50% of the population is)

2. You need to know what the LD50 (lethal dose in 50% of the population) is)

3. The spread between the ED50 and LD50 will provide you with an indication of the safety profile of the drug. If it`s a narrow therapeutic drug that difference between the LD50 and ED50 will be smallish and the dose that is effective and can be lethal is very close to one another and you need to be very careful on controlling the dosage..

4. You need to understand whether maintaining a steady-state concentration of the drug is desirable (the blood levels are maintained in a narrow band) - as is the case with Antibiotics to ensure a proper and effective kill rate of pathogens or if it should be dosed in a classic bell curve where it rises and falls giving your body a chance to rest which is typically 3x the half-life. For a 4hr t1/2, you would be prescribed 2x BID (twice a day) or every 12 hours.

5. Steady State: If you dose the drug at the half-life, after 5 doses, you`ll achieve steady whereby the plasma levels of the drug hardly change over the duration of the half-life.

6. Loading Dose: If you dose 2x the normal dose the 1st time, you decrease the amount of time it takes to his steady-state. Normally only need for a very fast elimation rate and need to hit steady-state fast (removal of a pathogen).

7. After 6-7 half-lifes (upon ending dosing), the drug is effectively removed from your system as you would have cleared over 99% of the drug and has no biological effect.

With hormones, from what I understand you do not want to be hitting steady-state and dosing on the half-life as you will cause several negative feedback loops and cause a cascade of hormonal responses that will have very negative consequences. That being said - there is probably very very few doctors or research papers are available on the effects of high constant levels of female hormones in biological males. I would guess that it would lead to several estrogen cancer concerns, a lose of sex drive, significant atrophy of testis and penis and probably a negative cognitive effect as well (decreased attentation etc.)

[chrishoney]

The T1/2 (half-life) of a drug you are correct that reflects the time a body requires to eliminate (or deactivate is better representation of what actually happens) 1/2 of the drug from your system.

Here are some important things to take into consideration when looking at T1/2:

1. You need to know what the ED50 (effective dose in 50% of the population is)

2. You need to know what the LD50 (lethal dose in 50% of the population) is)

3. The spread between the ED50 and LD50 will provide you with an indication of the safety profile of the drug. If it`s a narrow therapeutic drug that difference between the LD50 and ED50 will be smallish and the dose that is effective and can be lethal is very close to one another and you need to be very careful on controlling the dosage..

Research has failed to establish a LD50 for PM, even though it has been attempted using animals models. See this search: http://scholar.google.com/scholar?hl=en&q=LD50+for+pueraria+mirifica&btnG=&as_sdt=1%2C39&as_sdtp=

As you note later, there are no good studies looking at the effects of estradiol in males let alone PM, so an ED50 seems highly speculative. Just from the reports on this forum, the ED seems to be extremely variable on an individual basis, with some being relatively sensitive while others highly resistant to the effects of PM/deoxymiroestrol. In any case, since research has failed to establish an LD50, the spread between each individual's ED50 and LD50 is perforce VERY wide, and hence relatively safe from a toxicity perspective.

4. You need to understand whether maintaining a steady-state concentration of the drug is desirable (the blood levels are maintained in a narrow band) - as is the case with Antibiotics to ensure a proper and effective kill rate of pathogens or if it should be dosed in a classic bell curve where it rises and falls giving your body a chance to rest which is typically 3x the half-life. For a 4hr t1/2, you would be prescribed 2x BID (twice a day) or every 12 hours.

That's OK if you truly need to give your body a "rest." Again, this is unknown with PM/deoxymiroestrol and likely unnecessary as explained below. (Also, 2x BID is redundant at best if not outright confusing, rather like saying ATM machine. The correct terminology would be PO BID.)

Also, desirability of maintaining a steady state will vary depending on an individual's responsiveness to PM and their respective goals. I think Bryony has arrived at distinctly different goals (than he even started out with) in taking PM from many other folks, and seems to require a higher ED with a more frequent administration schedule. It seems as if with his physiology and goals he needs a steady state.

With hormones, from what I understand you do not want to be hitting steady-state and dosing on the half-life as you will cause several negative feedback loops and cause a cascade of hormonal responses that will have very negative consequences.

There is a great deal of controversy on just this topic in the MtF transgender community. From the accounts I have read, it seems like most TS women report better long term results when they attempt to maintain something like a steady state level of estradiol administration. Depending on administration method, most probably do have some kind of cycling of serum hormone levels rather than a true steady state, but it is also almost certainly a much shorter cycle than natal women experience. Many, if not most TS women maintain this administration schedule over years with no apparent deleterious effects. Physician monitoring of HRT dosages via serum hormone levels is often done on a quarterly or semi-annual basis with a consistent administration schedule considered optimal in each interval. This seems pretty close to a steady state to me.

This is my subjective evaluation of subjective reports I have read, as you are right, there are few if any studies looking at this. Do remember that the goals of a TS woman are physiologically different than a natal woman whose monthly cycle with its ebb and flow of hormone levels serves a biological purpose that males and TS women are unable to achieve. Experience suggests it is NOT necessary to mimic that cycle to achieve and maintian partial or complete feminization in males.

That being said - there is probably very very few doctors or research papers are available on the effects of high constant levels of female hormones in biological males. I would guess that it would lead to several estrogen cancer concerns, a lose of sex drive, significant atrophy of testis and penis and probably a negative cognitive effect as well (decreased attentation etc.)

In my opinion, except for the part regarding atrophy of the testes, the rest of that last part is largely urban myth. Reduced sex drive is very variable on an individual basis and the penis does not actually atrophy. The ability to continue to achieve erections is also highly variable, with many reporting no decrease in tumescence or length.

Any increased estrogen-sensitive cancer risk comes mainly from use of synthetic estrogens (such as DES, Premarin and few others) in combination with synthetic progestins (as versus bio-identical, micronized progesterone.) Bio-identical estradiol and micronized progesterone either alone or in combination do NOT have the same health risks as synthetics, and from all the evidence I have come across so far, PM apparently shares this low risk for negative side effects.

While it seems apparent from research that estradiol and testosterone affect distinct cognitive domains, I think it is a reach to consider the evidence for "negative" effects conclusive. Saying there are negative effects of estrogenic compounds on cognition would also imply that natal female cognitive strengths are "negative" in comparison to male cognitive strengths. Again, in my opinion this is not validated by research.

Finally, we are talking about an estrogen mimic, not pharmaceutical or even bio-identical hormones. While PM exhibits high estrogenic activity (http://scholar.google.com/scholar?q=estrogenic+activity+of+pueraria+mirifica&btnG=&hl=en&as_sdt=0%2C39) it is not a given that it behaves exactly the same as estradiol in all ways, though I suppose a conservative interpretation would be to think of it that way until proven otherwise.

[LookingForward2NBE]

With respect to Steady-State vs. flucating daily rhytms of hormones. Estrogen levels during sleep are quite low when compared to peak concentrations which are typically around 6-7am in the morning and then drop to its low level by mid-day and stay at the level. From the morning high to evening low, it's a 300-400% difference. There are flucuations through the day but as a mean of the top and bottom levels it rises quickly to a peak and then falls off. Maintaining a tight, steady-state concentration by dosing on the T1/2 is definitely altering the natural rhythm of a females cycle (even for NBE). I do not believe SS should be a suggested approach - especially for a female. As for a male, it's a relatively new and poorly charter territory.

I guess its up to each individual to decide if they want to:

1. Maintain a constaint steady-state level all day (then taking PM every 4hrs may be the best approach) in which case the common 2x day dosing is inadequate. However, splitting the the RDI amount into 4 doses will cause your Cmax (maximum blood concentration) to drop significantly so that may affect the Therapeutic window. Thereby, having to increase your RDI to get an equivalent or near equivalent Cmax which will lead to a higher total AUC (area under the curve). Leading to higher extent of absorption but not necessary therapeutic effect. The high extent of absorption could lead to increase prevalence of side affects which is typically associated with Total Exposure - amount of product. Just because something is "deactivated" does not means its eliminated, its conjugated into a non-functional component which is then eliminated but even the inactivated compound could still cause toxicity.

2. Dose like a natural response and take a single dose at waking vs. a split dose taken in 2 doses 12hrs apart.

3. Or taking a single dose between 9am-12pm, when your natural level begins to drop to have a higher elevated amount all day but still allowing your system a rest period late afternoon and throughout your sleep period.

4. Or taking a dose in the morning and a dose afternoon as is typically recommended, thereby decreasing the amount of rest to strictly during the sleep period.

The more I consider my personal program and approach, I'll probably start out 1x per day, late in the morning to give myself a "boosting" effect of Estrogen like activity and delaying the drop for 2-3hrs later into the day and potentially, a smaller dose at 5pm so as to get 50% of the dose out by 9 and 75% of it out by 12midnight.

I guess thats also a consideration for some who are poor responders to PM, changing their dosing time and approach could potentially have a significant impact depending on how their individual diurnal cycle is happening. Maybe going from 1 capsule 2x day to 1.5caps once day may lead to better outcomes and the time of the dose from either 6-7am or 10am-12pm or even after 5pm. Or taking 1/2 capsule 4x per day etc.

From the very very little bit of reading I have done male transformation, knocking out Test (by SP or other means) and dramatically increasing Estrogen will absolutely cause testicular shrinkage (due to lack of activity by the leydig cells i believe ie use it or lose it). With respect to Penis atrophy, the lack of nocturnal erections and lack of sex drive experienced by many when transitioning to predominately female based hormones (irregardless of they are synthetic Estrogen's or phytoestrogens). However, probably not an issue either way but I do not even begin to understand or appreciate the pyschological impact that such an individual is going through. As a man ages after 40-50, the penis does atrophy due to the lose of nocturnal erections due lower hormone levels (GH and Test).. slowly but it does. I recall reading somewhere that it can be by as much as 1/2 or more loss in length and rigidity. But that data was pre-Viagara type products. I guess men transitioning to women do also see the changes unless they are not on female hormone replacement therapy or still masturbate or have sex frequently. I guess even within that community, there are different levels of transgenders feminization...

[AbiDrew85]

With respect to Steady-State vs. flucating daily rhytms of hormones. Estrogen levels during sleep are quite low when compared to peak concentrations which are typicall around 6-7am in the morning and then drop to its low level by mid-day and stay at the level. From the morning high to after average low, it's a 300-400% difference. There are flucuations through the day but as a mean of the top and bottom levels it peaks and then falls off. Maintaining a tight, steady-state concentration by dosing on the T1/2 is definitely altering the natural rhythm of a females cycle and even for NBE, I do not believe should be a suggested approach - especially for a female. As for a male, it's a relative new and poorly charter territory.

Wow. Seems I've been doing myself good and didn't even know it. I had no idea about the diurnal cycle. Only the monthly. But I've been dosing in full as soon as I wake up with my PM extract. My goals are to actually attempt to fully emulate a female cycle. It is my belief that this is the ideal for me personally, some of the reasons for that I'll go into below.

From the very very little bit of reading I have done male transformation, knocking out Test (by SP or other means) and dramatically increasing Estrogen will absolutely cause testicular shrinkage (due to lack of activity by the leydig cells i believe ie use it or lose it). With respect to Penis atrophy, the lack of nocturnal erections and lack of sex drive experienced by many when transitioning to predominately female based hormones (irregardless of they are synthetic Estrogen's or phytoestrogens). However, probably not an issue either way but I do not even begin to understand or appreciate the pyschological impact that such an individual is going through. As a man ages after 40-50, the penis does atrophy due to the lose of nocturnal erections due lower hormone levels (GH and Test).. slowly but it does. I recall reading somewhere that it can be by as much as 1/2 or more loss in length and rigidity. But that data was pre-Viagara type products. I guess men transitioning to women do also see the changes unless they are not on female hormone replacement therapy or still masturbate or have sex frequently. I guess even within that community, there are different levels of transgenders feminization...

That research is actually kind of divisive. There's segments of the transgender community who perhaps aren't QUITE as "female" as others who yes, they lose sex drive and all sexual functionality on HRT. Then there's those that it kinda just lessens a little, but it's still there. And then there's the ones who respond like me, and when they're given even just a little bit of E and their T is being fully suppressed their sex drive goes through the roof - just like, I might point out, a genetic woman.

It is my belief that the lattermost group of which I am a part of would and do benefit most from simulating a regular female cycle as closely as possible.

The other groups? I doubt it matters too much either way. Though I suspect they'll get better physical transformations through emulating the female cycle. After all, we all too often see women with no or very irregular periods who're underdeveloped. We also tend to see a high proportion of underdeveloped T-girls. I do not believe that correlation to be a coincidence.

[karen]

I went back to the excerpt that I saved from the paper and slowly read it over again.

I screwed up ... the half-life number of 3.2/4.2 was NOT for Miroestrol it was for Genistein ....

I apologize for misleading anyone on the half-life numbers .... the concept that 1/2 life affects how often one should take a drug/herb IS CORRECT ... but the 3.2/4.2 hour numbers are NOT.

I'll see if I can find any valid numbers

Again ... Sorry .... Karen

[bryony]

Regarding the discussion on penis atrophy, I believe the theory that the cause is due to failing erections. The effect of PM (for me) was such that stimulation of the penis alone lost its attraction. For the first few months of PM use, my penis did appear to be shrinking.

After that period, however, my breasts became extremely erogenous, and it has become actually impossible to be unaware of them; even the touch of my t-shirt as I move is sufficient to stimulate them.

It requires very little, even tiny amounts of breast stimulation now to ensure that my penile atrophy has ceased and reversed itself somewhat.

I imagine not everyone will experience these effects, however!

B.

[flamesabers]

The effect of PM (for me) was such that stimulation of the penis alone lost its attraction.

I have observed the same with myself. I see this as being a physical and mental diminishing of my sex drive.

For the first few months of PM use, my penis did appear to be shrinking.

After that period, however, my breasts became extremely erogenous, and it has become actually impossible to be unaware of them; even the touch of my t-shirt as I move is sufficient to stimulate them.

I was never keen on measuring myself so I'm not sure whether there has been any shrinkage or not. My breasts haven't become erogenous in the slightest.